| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| KCNQ2 | R581G | Infantile spasms | Medium | 2 | 25262651 |
| KCNQ2 | R581X | Epilepsy, benign neonatal | Medium | 2 | 14534157, 25525159 |
To assess whether the paralogue annotation here confidently predicts that variation at this residue is pathogenic, it is important to check the reports in the Pubmed links above to ascertain that the mutations in these paralogues have been proved likely to be disease-causing. It is also important to check that the direction of effect of the variant in the paralogue is compatible with your observed phenotype in KCNQ1.
| KCNQ1 | AKKKFQQARKPYDVRDVIEQYSQGHLNLMV>R<IKELQRRLDQSIGKPSLFIS---------- | 575 |
| KCNQ2 | SKRKFKESLRPYDVMDVIEQYSAGHLDMLS>R<IKSLQSRVDQIVGRGPAITD--KDR--T-- | 605 |
| KCNQ3 | YKKKFKETLRPYDVKDVIEQYSAGHLDMLS>R<IKYLQTRIDMIFTPGPPSTP--KHKKSQKG | 588 |
| KCNQ4 | AKRKFKETLRPYDVKDVIEQYSAGHLDMLG>R<IKSLQTRVDQIVGRGPGDRKAREKG--D-- | 601 |
| KCNQ5 | AKRKFKETLRPYDVKDVIEQYSAGHLDMLC>R<IKSLQTRVDQILGKGQITSD-KKSR--E-- | 588 |
| KCNA1 | ------------------------------>-<------------------------------ | |
| KCNA10 | ------------------------------>-<------------------------------ | |
| KCNA2 | ------------------------------>-<------------------------------ | |
| KCNA3 | ------------------------------>-<------------------------------ | |
| KCNA4 | ------------------------------>-<------------------------------ | |
| KCNA5 | ------------------------------>-<------------------------------ | |
| KCNA6 | ------------------------------>-<------------------------------ | |
| KCNA7 | ------------------------------>-<------------------------------ | |
| KCNB1 | ------DPSPLLPVLGMYHDPLRNRGSAAA>A<VAGLECA----------------------- | 711 |
| KCNB2 | GSAPQTPPSTARPLPVTTADFSLTTPQHIS>T<ILLEETP----------------------- | 761 |
| KCNC1 | GEYACPPGGGMRK----------DLCKESP>-<--VIAKY----------------------- | 576 |
| KCNC2 | GDYTCASDGGIRKG----YEKSRSLNNIAG>L<AGNALRL----------------------- | 614 |
| KCNC3 | -DYAPSPDGSIRKATGAPPLPPQDWRKPGP>P<S-FLPDL----------------------- | 747 |
| KCNC4 | GDYACA-DGSVRKG----TFVLRDLPLQHS>P<---EAAC----------------------- | 624 |
| KCND1 | LA--GLRRSHAPQSRSSLNAKPHDSLDLNC>D<SRDFVAA----------------------- | 597 |
| KCND2 | IQIRCVERTPLSNSRSSLNAKMEECVKLNC>E<QPYVTTA----------------------- | 596 |
| KCND3 | IHIQGSEQPSLTTSRSSLNLKADDGLRPNC>K<TSQITTA----------------------- | 613 |
| KCNF1 | ------------------------------>-<------------------------------ | |
| KCNG1 | ------------------------------>-<------------------------------ | |
| KCNG2 | ------------------------------>-<------------------------------ | |
| KCNG3 | ------------------------------>-<------------------------------ | |
| KCNG4 | ------------------------------>-<------------------------------ | |
| KCNS1 | ------------------------------>-<------------------------------ | |
| KCNS2 | ------------------------------>-<------------------------------ | |
| KCNS3 | ------------------------------>-<------------------------------ | |
| KCNV1 | ------------------------------>-<------------------------------ | |
| KCNV2 | ------------------------------>-<------------------------------ | |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.R555C | c.1663C>T | Inherited Arrhythmia | LQTS | rs120074185 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | KVLQT1 C-terminal missense mutation causes a forme fruste long-QT syndrome. Circulation. 1997 96(9):2778-81. 9386136 | ||
| Inherited Arrhythmia | LQTS | Catecholamine-provoked microvoltage T wave alternans in genotyped long QT syndrome. Pacing Clin Electrophysiol. 2003 26(8):1660-7. 12877697 | |||
| Inherited Arrhythmia | LQTS | Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients. J Mol Med (Berl). 2004 82(3):182-8. 14760488 | |||
| Inherited Arrhythmia | LQTS | Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing. Heart Rhythm. 2005 2(5):507-17. 15840476 | |||
| Inherited Arrhythmia | LQTS | Kv7.1 (KCNQ1) properties and channelopathies. J Physiol. 2008 586(7):1785-9. 18174212 | |||
| Inherited Arrhythmia | LQTS | Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. Heart Rhythm. 2009 6(9):1297-303. 19716085 | |||
| Inherited Arrhythmia | LQTS | PKA and PKC partially rescue long QT type 1 phenotype by restoring channel-PIP2 interactions. Channels (Austin). 2010 4(1):3-11. 19934648 | |||
| Inherited Arrhythmia | LQTS | Impaired KCNQ1-KCNE1 and phosphatidylinositol-4,5-bisphosphate interaction underlies the long QT syndrome. Circ Res. 2005 96(7):730-9. 15746441 | |||
| Inherited Arrhythmia | LQTS | Mutations in cytoplasmic loops of the KCNQ1 channel and the risk of life-threatening events: implications for mutation-specific response to β-blocker therapy in type 1 long-QT syndrome. Circulation. 2012 125(16):1988-96. 22456477 | |||
| Inherited Arrhythmia | LQTS | A long QT mutation substitutes cholesterol for phosphatidylinositol-4,5-bisphosphate in KCNQ1 channel regulation. PLoS One. 2014 9(3):e93255. doi: 10.1371/journal.pone.0093255. eC 24681627 | |||
| Inherited Arrhythmia | LQTS | Long QT mutations at the interface between KCNQ1 helix C and KCNE1 disrupt I(KS) regulation by PKA and PIP₂. J Cell Sci. 2014 127(Pt 18):3943-55. doi: 10.1242/jcs.147033. 25037568 | |||
| Inherited Arrhythmia | LQTS | Properties of KvLQT1 K+ channel mutations in Romano-Ward and Jervell and Lange-Nielsen inherited cardiac arrhythmias. EMBO J. 1997 16(17):5472-9. 9312006 | |||
| p.R555H | c.1664G>A | Inherited Arrhythmia | LQTS | rs199472800 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | Long QT syndrome in neonates: conduction disorders associated with HERG mutations and sinus bradycardia with KCNQ1 mutations. J Am Coll Cardiol. 2004 43(5):826-30. 14998624 | ||
| Inherited Arrhythmia | LQTS | Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing. Heart Rhythm. 2005 2(5):507-17. 15840476 | |||
| Inherited Arrhythmia | LQTS | Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. Heart Rhythm. 2009 6(9):1297-303. 19716085 | |||
| Inherited Arrhythmia | LQTS | Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009 120(18):1752-60. 19841300 | |||
| Inherited Arrhythmia | LQTS | [Neonatal forms of congenital long QT syndrome]. Arch Mal Coeur Vaiss. 2004 97(5):479-83. 15214551 | |||
| Inherited Arrhythmia | LQTS | Phylogenetic and physicochemical analyses enhance the classification of rare nonsynonymous single nucleotide variants in type 1 and 2 long-QT syndrome. Circ Cardiovasc Genet. 2012 5(5):519-28. doi: 10.1161/CIRCGENETICS.112.963785. 22949429 | |||
| Inherited Arrhythmia | LQTS | Long QT mutations at the interface between KCNQ1 helix C and KCNE1 disrupt I(KS) regulation by PKA and PIP₂. J Cell Sci. 2014 127(Pt 18):3943-55. doi: 10.1242/jcs.147033. 25037568 | |||
| Inherited Arrhythmia | LQTS | LQT1 mutations in KCNQ1 C-terminus assembly domain suppress IKs using different mechanisms. Cardiovasc Res. 2014 104(3):501-11. doi: 10.1093/cvr/cvu231. 25344363 | |||
| p.R555S | c.1663C>A | Inherited Arrhythmia | LQTS | rs120074185 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. Heart Rhythm. 2009 6(9):1297-303. 19716085 | ||